Marian Freedman

A study of lisdexamfetamine dimesaylate (LDX) in children aged 4 to 5 years with attention-deficit/hyperactivity disorder (ADHD) found that the treatment reduced symptoms and was generally well tolerated compared with placebo.

The study’s 199 participants had baseline scores on the parent-reported ADHD Rating Scale-IVPreschool Version (ADHD-RS-IV-PS) and the Clinical Global Impression-Improvement (CGI-I) scale. Scores on these 2 scales, determined again at the end of the 6-week study period, provided the major end points for the trial. Most (175) of the participants had diagnoses of the combined ADHD subtype and CGI scores corresponding to “markedly ill.” Only 8 of the participants had used ADHD medications, such as atomoxetine, guanfacine, and methylphenidate, prior to being in the study.

Participants were divided into 2 groups. One group received LDX for 6 weeks and the other group received placebo. Some children received 5 mg of LDX or matching placebo while others received 10-, 20-, or 30-mg doses. At the end of the 6-week study period, CGI-I scores had improved in 41.7% of patients in the LDX group compared with 24.3% of patients in the placebo group. As for ADHD-RS-IV-PS, the LDX group did better than the placebo group with regard to inattention but not with regard to hyperactivity/impulsivity. Almost half the participants in the active group had adverse effects, usually mild. These adverse effects most often included decreased appetite and irritability.

Lisdexamfetamine is converted to the less expensive dextroamphetamine, known to be effective for ADHD, so these results are expected. I do not like the trend of using stimulants to treat preschool-aged patients, even if they are effective, and suspect this study will be used to push for lowering the approved age for use. Also of note is the high incidence of adverse effects.

Childress AC, Lloyd E, Jacobsen L, Gunawardhana L, Johnson SA Jr, Findling RL. Efficacy and safety of lisdexamfetamine in preschool children with attention-deficit/hyperactivity disorder. 

Published online May 13, 2022. doi:10.1016/j.jaac.2022.03.034

Articles

Lisdexamfetamine dimesaylate was associated with reduced ADHD symptoms in children aged 4 to 5 years.

Lisdexamfetamine is effective in preschoolers with ADHD

A digitally delivered sleep strategy (ie, an app) based on cognitive behavioral therapy (CBT) approaches can reduce childhood sleep problems. This was the finding of a pilot study that investigators conducted after first determining in a preliminary pilot study that new tools are needed to address pediatric sleep problems.

In the first study, about three-fourths (74%) of 218 participants (or their parents) reported sleep problems, usually mild (40.7%) or moderate (24.7%). Participants in the first study were aged 18 years or younger. Parents most often sought help for these problems by consulting their pediatrician (62%), a book (57%), a friend/family member (48%), a sleep consultant (41%), or web search (36%). Almost one-third (30%) of participants indicated the solution they tried did not produce meaningful improvements. Although only 8% of parents found their child’s sleep problems severely distressing, 41% termed them moderately distressing. Sleep problems also were associated with significant monetary costs.

In a second pilot study, investigators enrolled 11 families with sleep problems to receive the mobile app, DrLullaby, which includes pediatric versions of CBT protocols for insomnia, such as sleep restriction, stimulus control, relaxation strategies, worry time, cognitive restructuring, maintenance, and relapse prevention along with training and behavioral management techniques for parents. Participant families were assigned various informational modules depending on the child’s specific sleep problems, with the expectation of completing 1 module each week for 6 to 10 weeks. Each module is linked to more detailed reading materials about the desired changes and instructions on how to implement them. Participants also completed a weekly sleep distress scale and a daily sleep log.

DrLullaby was associated with improvements in key sleep behaviors, including time to fall asleep (72.7%), total time asleep (54.5%), and time awake (63.6%). These figures represent a mean 31.3% and 75.6% change from baseline for time to fall asleep and time awake, respectively, along with a mean improvement of 1 hour and 3 minutes compared with baseline for total time asleep. In addition, the collective distress scale score fell by 35%.

This is a small study of 11 children, 10 of whom were not infants (ages not specified), so it is not known whether the results will stand up. However, it may be worth looking into further; 6 to 8 weeks of treatment would cost $20 to $30. Some of the authors of the study are affiliated with the company that makes the app, suggesting potential conflicts of interest.

Tedford SE, Romano L, Gozal D, Medalie L. Digital solutions for sleep problems in children: a pilot study. 

 2022;57(8):1914-1920. doi:10.1002/ppul.25402

A digital sleep strategy may reduce sleep problems for children.

Need more sleep? Digital solutions show promise

Children with type 1 diabetes (T1D) have similar bone mineral density (BMD) levels to children without the disease, according to findings from a cross-sectional, case-control study conducted in an outpatient clinic in India. However, those with T1D had lower vitamin D levels than their peers without T1D, the study results showed.

Study participants were 37 children with T1D (mean age of 10 years) who require insulin to maintain normal blood glucose level and 37 children without T1D (mean age of 9.7 years). All participants underwent dual-energy x-ray absorptiometry scan of the lumbar spine and measurements of various bone health parameters, such as serum osteocalcin level, deoxypyridinoline level, serum vitamin D level, phosphorus and calcium levels, and alkaline phosphatase level.

Only 3 children with T1D (8%) had a low BMD level compared with none in the control group. However, serum 25-hydroxyvitamin D (25[OH]D) level was significantly lower in the T1D group than in the control group, and serum-intact parathyroid hormone level was substantially higher. Bone mineral content was similar in the 2 groups, as were all other bone turnover variables.

Children with T1D have enough to worry about; it is reassuring we can cross BMD off the list (at least in childhood). Vitamin D supplementation has been called into question recently but given the elevated parathyroid hormone levels seen in the study results, it seems worth reconsidering.

Kumar RA, Kumar CGD, Sahoo J. Evaluation of bone mineral density in children with type 1 diabetes: a cross-sectional case–control study.

. 2022;2(1):9-13. doi:10.25259/JPED_1_2022

A study found similar bone mineral density between children with and without type 1 diabetes.

Type 1 diabetes and low bone mineral density are not a common combination

Swedish researchers found that many children and young adults who are prescribed melatonin are still taking it 3 years later and at larger doses.

Using registry data for an urban area centered around Stockholm, the authors determined that 9980 individuals up to aged 25 years were dispensed melatonin in 2016. Most patients (65%) had a neuropsychiatric diagnosis, and only 20% had a sleep disorder.

Prevalence of dispensed melatonin was 0.2% in preschoolers 5 years and younger, 1.4% in children aged 6 to 12 years, 3.4% in adolescents aged 13 to 17 years, and 1.2% in those aged 18 to 25 years.

Comorbid conditions were common, as was polypharmacy, identified in 4567 individuals (46%), more often females than males. Of those who began taking melatonin in 2016, 50% of male patients and 40% of female patients continued to use it throughout the following 3 years, often at increased doses.

I, too, would like to see some long-term studies. But given that sleep difficulties are major problems for children and their families, especially when combined with developmental disabilities such as autism, I continue to use melatonin in high doses if needed for these families. For neurotypical children, however, my go-to remains behavioral interventions.

Tedroff K, von Euler M, Dahlén E. Melatonin usage in children and young adults, a registry-based cohort study. 

 2022;39(30-34). doi:10.1016/j.ejpn.2022.05.007

Many children continue to use melatonin for years after being prescribed the medication, according to a recent study.

Long-term melatonin use in children: Is it safe? 

Only 3.6% of fully vaccinated febrile children with sickle cell disease (SCD) who visited an emergency department were found to have a serious bacterial infection (SBI) meriting hospitalization, according to a retrospective study in Saudi Arabia.

Investigators screened medical records associated with 833 febrile events, resulting in 40 study participants with positive bacterial culture results from various body fluids. The authors assessed the 30 febrile events for the remaining children and concluded that their hospitalization was justified. All these children were younger than 12 years and had received recommended vaccinations, including 13-valent pneumococcal conjugate vaccine, quadrivalent meningococcal conjugate vaccine, and 

type b vaccine, as well as regular penicillin prophylaxis. Additionally, most (57%) participants were male.

Urinary tract infection was the most prevalent SBI, seen in 2.2% of participants, followed by bacteremia (1.3%), osteomyelitis (0.24%), and meningitis (0.12%). Pneumococcus was the most common organism associated with bacteremia (46%), followed by Salmonella species (36%). All the children recovered.

The authors concluded that as the prevalence of SBI continues to decline in patients with SCD, ambulatory management using empirical antibiotics often is appropriate.

Before we had the many immunizations now available, as well as ceftriaxone, febrile children with SCD were hospitalized for several days routinely, regardless of how well they appeared. This study offers further support for treating such children as outpatients, provided they do not appear toxic and one can establish good follow-up.

Frequency of serious bacterial infection among febrile sickle cell disease children in the era of the conjugate vaccine: A retrospective study. 

International Journal of Pediatrics and Adolescent Medicine. 

Published online May 31, 2022. doi:10.1016/j.ijpam.2022.05.002

With instances of SBI lowering in children with sickle cell disease, authors of a recent study recommended continued management through empirical  antibiotics.

Prevalence of SBI in children with sickle cell disease continues to decline

MRI revealed inflammatory features in the ankle and midfoot of children with a clinical diagnosis of arthritis, not only in those with juvenile idiopathic arthritis (JIA), but also in those who did not have a final JIA diagnosis, according to a retrospective case-control study.

The single-center study was conducted at a center for pediatric rheumatology in Poland in 44 children aged 5 to 16 years (35 girls and 9 boys) with clinically suspected active ankle arthritis. Participants’ symptoms included ankle pain, swelling, tenderness, or limitation of movement associated with pain persisting more than 6 weeks. All participants underwent an MRI of the ankle that covered the area from the tibiotalar joint to the metatarsophalangeal joints.

JIA was confirmed in 22 (50%) of study group participants, including 14 patients with oligoarthritis, 6 with undifferentiated JIA, 1 with systemic JIA, and 1 with enthesitis-related arthritis. More lesions were identified in the JIA group than in the non-JIA group, with only 6 children free of lesions: 2 (4.5%) in the JIA group and 4 (9.0%) in the non-JIA group. MRI revealed inflammatory features in 38 (86%) of total study patients. No significant differences were found in either gender or mean age between the JIA group and the non-JIA group. The duration of arthritis in JIA patients ranged from 5 to 144 months (mean, 35.41 months) and in non-JIA patients from 6 to 36 months (mean, 17.6 months).

The most common findings in both groups were effusion in the tibiotalar joint (68% in the JIA group vs 64% in the non-JIA group) and effusion in the subtalar joint (64% vs 59%, respectively). However, tenosynovitis was the only lesion that was significantly more common in the JIA group than in the non-JIA group. In addition, advanced active inflammatory lesions were diagnosed in more than half (55%) of the JIA group and in none of the non-JIA group.

JIA remains an elusive diagnosis to pin down at times; it traditionally is based on a variety of factors, with no pathognomonic findings. There may be valid reasons for ordering an MRI of the ankle in these patients, but using the MRI to make a diagnosis is not one of them.

Ostrowska M, Michalski E, Gietka P, Mańczak M, Posadzy M, Sudoł-Szopińska I. Ankle magnetic resonance imaging in juvenile idiopathic arthritis versus non-juvenile idiopathic arthritis patients with arthralgia. 

. 2022;11(3):760. doi:10.3390/jcm11030760

In a recent study, rate of ankle arthritis did not differ significantly between children with JIA and children without JIA.